The pentapeptide thymopentin is the active site of the naturally-occurring polypeptide thymopoietin. Both thymopoietin and thymopentin induce biological changes in two human T cell lines, MOLT-4 and CEM, thereby indicating their roles in stimulating helper and suppressor activities of T cells. The naturally-occurring polypeptide thymopoietin has been detected in basal cells of skin, although its function is uncertain [See, e.g., A. C. Chu et al, J. Invest. Dermatol., 81:194 (1983)].
U.S. Pat. No. 4,190,646 discloses thymopentin as well as peptide compositions in which various groups are substituted onto the amino and/or carboxyl termini of this pentapeptide. See also, for example, G. Goldstein, Nature (London) 247: 11-14 (1974); R. S. Basch and G. Goldstein, Proc. Natl. Acad. Sci. U.S.A., 71:1474-1478 (1974); M. P. Scheid et al., J. Exp. Med., 147:1727-1743 (1978); M. P. Scheid et al., Science, 190:1211-1213 (1975); G. E. Ranges et al., J. Exp. Med., 156:1057-1064 (1982); T. Audhya et al., Biochem. 20:6195-6200 (1981); K. Venkatasubramanian et al., Proc. Natl. Acad. Sci. U.S.A., 83:3171-3174 (1986); M. G. Malaise et al., in "Immunoregulatory UCLA Symposium on Molecular and Cellular Biology", eds. G. Goldstein et al., (Liss, New York) (1986); G. G. Sunshine et al., J. Immunol., 120:1594-1599 (1978) and E. Rentz et al., Arch. Geschwulstforsch, 54(2):113-118 (1948). See also U.S. Pat. Nos. 4,261,886; 4,361,673; 4,420,424; and 4,629,723. Reference is made to the above-described patents, applications and articles for a discussion of other background material and the biological processes involved in the present invention.
Thymopentin has been developed for pharmaceutical administration as a parenteral drug, and has proved valuable in treating systemically certain chronic infections characterized by an immunosuppressed state of the host. Conditions for which thymopentin has been employed therapeutically include lepromatous leprosy and severe recurrent herpes virus infections. This pentapeptide has also been employed in the treatment of certain allergies. Thymopentin has additionally been studied for the systemic treatment of atopic dermatitis.
Thymopentin has proved to be an outstandingly safe therapeutic agent for systemic parenteral administration in both a wide range of animal studies and extensive clinical trials for these and other conditions. [See, e.g., E. Sundal et al., "Therapy with thymopentin: A clinical overview", in Immune Regulation by Characterized Peptides, eds: G. Goldstein et al., Alan R. Liss, Inc. N.Y., pp 121-136 (1987); A. Castells et al., Surv. Immunol. Res., 4:63-69, Suppl. 1 (1985); J. Demaubeuge et al, Surv. Immunol. Res., 4:30-36, Suppl. 1 (1985); co-owned, copending U.S. patent application Ser. No. 822,704; N. Friedmann, Surv. Immunol. Res., 4:139-154 Suppl. 1 (1985)].
Thymopentin has also been employed in experimental therapy with patients having acquired immunodeficiency syndrome, or AIDS, a disease predominantly caused by transmission of the retrovirus, HIV-1, and with a category of patients demonstrating symptoms of AIDS related complex, or ARC. [See, e.g., N. Clumeck et al., Int. J. Clin. Pharm. Res., 4:459-463 (1984); W. Barcellini et al., Clin. Exp. Immunol., 67:537-543 (1987)]
There has been no suggestion to date that thymopoietin or thymopentin are useful as other than systemically acting pharmaceutical agents for parenteral or intravenous administration.